Circulating biomarkers are associated with disease severity of chronic hand eczema and atopic dermatitis.

BACKGROUND: Although chronic hand eczema (CHE) is a highly prevalent and disabling skin disease, it is currently unknown if CHE is associated with systemic inflammation. OBJECTIVES: To characterize the plasma inflammatory signature of CHE. METHODS: Using Proximity Extension Assay technology, we assessed 266 inflammatory and cardiovascular disease risk proteins in the plasma of 40 healthy controls, 57 patients with atopic dermatitis (AD) with active lesions, 11 with CHE and a history of AD (CHEPREVIOUS_AD), and 40 with CHE and no history of AD (CHENO_AD). Filaggrin gene mutation status was also assessed. Protein expression was compared between groups and according to disease severity. Correlation analyses for biomarkers, and clinical- and self-reported variables, were performed. RESULTS: Very severe CHENO_AD was associated with systemic inflammation when compared with controls. Levels of T helper (Th)2- and Th1-, general inflammation and eosinophil activation markers increased with severity of CHENO_AD, primarily being significantly increased in very severe disease. Significant, positive correlations were found between markers from these pathways and severity of CHENO_AD. Moderate-to-severe but not mild AD displayed systemic inflammation. The Th2 markers C-C motif chemokine (CCL)17 and CCL13 (also known as monocyte chemotactic protein 4) were the top differentially expressed proteins in both very severe CHENO_AD and moderate-to-severe AD, showing a higher fold change and significance in AD. CCL17 and CCL13 levels further correlated positively with disease severity in both CHENO_AD and AD. CONCLUSIONS: Systemic Th2-driven inflammation is shared between very severe CHE with no history of AD, and moderate-to-severe AD, suggesting that Th2 cell targeting could be effective in several CHE subtypes.

Ten-year trends in contact allergy to formaldehyde and formaldehyde-releasers.

BACKGROUND: Preservatives such as formaldehyde and formaldehyde-releasers are common causes of contact allergy. OBJECTIVES: To examine trends in contact allergy to formaldehyde and formaldehyde-releasers in patch tested patients in Denmark over a 10-year period (2007-2016), and to investigate relevant sources of formaldehyde among the patients. METHODS: A cross-sectional registry study on patch test data from patients tested with formaldehyde and formaldehyde-releasers (N = 8463) was performed. The presence of released formaldehyde in products from formaldehyde-allergic patients was identified with chemical analyses (chromotropic acid or acetylacetone test). RESULTS: The prevalence of contact allergy to formaldehyde 1% was 1.5%, and ranged between 0.97% and 2.3%, with a decreasing trend in this 10-year period. Contact allergy to formaldehyde 2% was found in 2.4%, and no significant trend was observed. Quaternium-15 was the formaldehyde-releaser most often positive (0.86%). Patients allergic to formaldehyde often had simultaneous positive patch test reactions to formaldehyde-releasers (36%). Almost 63% of the patients with formaldehyde allergy used products that released formaldehyde; cosmetics were the most common sources. CONCLUSIONS: Although contact allergy to formaldehyde 1% decreased in this 10-year time period, contact allergies to formaldehyde and formaldehyde-releasers overall remain frequent in patients. In most cases, formaldehyde-allergic patients are exposed to ≥1 products containing formaldehyde. Improved regulation on permitted amounts of free formaldehyde in cosmetics is still warranted, including direct labelling of formaldehyde when it is present in small but relevant amounts.

The Proteome of Hand Eczema Assessed by Tape Stripping.

Hand eczema (HE) is a prevalent skin disease. However, the classification of HE into different subtypes remains challenging. A limited number of previous studies have employed invasive biopsy-based strategies; yet, studies of the HE proteome using noninvasive tape-stripping methodology have not been reported. In this study, we wanted to assess whether global proteomic analysis of skin tape strip samples can be used for subclassification of patients with HE. Tape strips were collected from patients with HE and healthy skin. Liquid chromatography-mass spectrometry proteomics was performed, and the global protein expression was analyzed. We identified 2,919 proteins in stratum corneum-derived skin cells from tape strip samples. Compared with healthy skin, the lesional samples from patients with HE exhibited increased expression of immune-related markers and a decreased expression of structural barrier proteins. The difference between HE subtypes was restricted to the lesional skin areas and included an increased expression of skin barrier-related proteins independently of the concurrent AD. In conclusion, we found that the noninvasive tape strip method used in combination with liquid chromatography-mass spectrometry proteomics can be used for analysis of skin protein expression in patients with HE. Thus, the method shows potential for assessing the proteomic differences between subtypes of HE and biomarker discovery.

The stratum corneum transcriptome in atopic dermatitis can be assessed by tape stripping.

BACKGROUND: Skin biopsies represent a gold standard in skin immunology and pathology but can cause pain and induce scarring. Non-invasive techniques will facilitate study recruitment of e.g. patients with paediatric atopic dermatitis (AD), hand eczema or facial dermatitis. OBJECTIVE: By RNA sequencing, we examined whether the stratum corneum transcriptome in AD skin can be assessed by tape stripping, as compared to the epidermal transcriptome of AD in skin biopsies. To make the procedure clinically relevant tape strips were stored and shipped at room temperature for up to 3 days. METHODS: Nine adult Caucasian AD patients and three healthy volunteers were included. Tape samples were collected from non-lesional and lesional skin. Biopsies were collected from lesional skin and were split into epidermis and dermis. Total RNA was extracted, and shotgun sequencing was performed. RESULTS: Shotgun sequencing could be performed on skin cells obtained from two consecutive tape strips which had been stored and shipped at room temperature for up to three days. The most prominent differences between the tape strip and biopsy derived transcriptome were due to structural genes, while established molecular markers of AD, including CCL17, CCL22, IL17A and S100A7-S100A9, were also identified in tape strip samples. Furthermore, the tape strip derived transcriptome showed promise in also analysing the skin microbiome. CONCLUSION: Our study shows that the stratum corneum (SC) transcriptome of AD can be assessed by tape stripping the skin, supporting that this method may be central in future skin biomarker research. NCBI GEO data accession: GSE160501.